Poor Recurrence-free Survival Research Articles

The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association

IntroductionBladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. Material and methodsA total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. ResultIn high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. ConclusionThe upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Association of BRAF V600E allele frequency with clinicopathologic outcomes in papillary thyroid cancer.

BRAF V600E mutation is the most common genetic driver of papillary thyroid cancer (PTC), where it is found with various allele frequency (AF), reflecting the proportion of cells carrying the mutant and wild-type gene alleles. To determine whether BRAF V600E AF can improve prognostication and inform initial surgical management of PTC. Retrospective cohort study (2016-2019). UCLA health. Consecutive patients with Bethesda V/VI nodules and isolated BRAF V600E mutation who underwent surgery with histopathology showing PTC. Blinded ThyroSeq v3 molecular analysis after completion of initial management and follow-up. Aggressive histopathology and cancer persistence/recurrence. Of 73 patients, the median BRAF V600E AF was 25.5% (IQR, 16.7-34.3%). Higher median AF was seen in patients classified as American Thyroid Association (ATA) high-risk (37%) vs. intermediate-risk (25.3%, p<0.01) and low-risk (24.7%, p<0.01), largely attributed to higher AF in patients with gross extrathyroidal extension (ETE) (40.1% vs. 25.2% without gross ETE, p=0.02). No differences in AF were observed on the basis of lymph node positivity or presence of aggressive variants of PTC. A higher BRAF V600E AF was also found in patients with tumors ≥2cm vs. <2cm (median 32.0% vs. 24.4%, p<0.01). Over 4.1 years of follow-up, disease persistence/recurrence was found in 7 patients (9.4%) and was associated with higher median AF than those without recurrence (35.3% vs. 25.2%, p=0.02). Higher AF was associated with poorer recurrence-free survival (AF≥35%, HR 7.40, CI 1.4-38.1). Higher AF was associated with gross ETE and increased recurrence risk. This may inform initial management in patients with PTC harboring an isolated BRAF V600E mutation.

CXCR6 expression predicts prognosis and immunotherapeutic benefit in muscle-invasive bladder cancer

BackgroundIncreasing evidence suggests that the CXC chemokine receptor 6 (CXCR6) is involved in tumor progression and the regulation of tumor immunity. However, its role in muscle-invasive bladder cancer (MIBC) remains largely unexplored.MethodsData from 391 MIBC patients in the TCGA, 212 patients from GEO, 131 patients from our center, 195 patients in the IMvigor210 cohort, and single-cell RNA sequencing (scRNA-seq) data from 9 bladder cancer patients (GSE222315) were analyzed. Additionally, data from the GEPIA 2, TISCH2, TIMER2.0, and UALCAN platforms were utilized to investigate the prognostic and immunotherapeutic significance of CXCR6 in MIBC.ResultsWe observed that CXCR6 expression was significantly reduced in bladder cancer tumors and correlated with tumor stage and grade. Low CXCR6 expression was associated with poor recurrence-free survival (RFS) and overall survival (OS) in the TCGA cohort, a finding validated in both the meta-GEO dataset and our center’s cohort. Multivariate analysis confirmed that low CXCR6 expression was an independent predictor of poor OS and RFS. A nomogram incorporating CXCR6 expression and other independent prognostic factors was developed to accurately predict 3- and 5-year OS. Gene set enrichment analysis indicated that immune activation-related pathways were significantly enriched in tumors with high CXCR6 expression. CIBERSORT analysis revealed that CXCR6 expression was positively correlated with CD8+ T cells, CD4+ T cells, activated NK cells, M1 macrophages, and activated dendritic cells in TCGA, findings further validated by TIMER2.0. scRNA-seq data showed that CXCR6 was predominantly expressed in T and NK cells and facilitated T/NK-myeloid interaction via the CXCR6-CXCL16 axis. Importantly, CXCL16+ macrophages and dendritic cells recruited CXCR6+ T and NK cells, which exhibited enhanced cytotoxicity, thereby amplifying anti-tumor immunity. Clinically, in the IMvigor210 immunotherapy cohort, higher CXCR6 expression was associated with improved anti-PD-L1 therapeutic outcomes.ConclusionOur findings highlight CXCR6 as a critical biomarker for predicting prognosis and immunotherapeutic response in MIBC.

Prognostic impact of circulating tumor DNA detection in portal and peripheral blood in resected pancreatic ductal adenocarcinoma patients

In PDAC patients, ctDNA detection’s prognostic significance needs validation especially in resected patients. This study investigated ctDNA kinetics in portal and peripheral blood before and after resection, and whether tissue mobilization during surgery influences ctDNA detection. In this single-center prospective cohort, portal and peripheral blood were drawn during pancreaticoduodenectomy before and after tissue mobilization, during 12 postoperative months and were associated with overall survival (OS), recurrence-free survival (RFS) and CA19-9 (secondary endpoints). Tumor mutations were identified using next-generation-sequencing and ctDNA detected by digital droplet PCR. From 2018 to 2022, 34 patients were included. The 2-year RFS and OS were 47.6%(95%CI[29.5; 63.6]) and 65.7%(95%CI[46.5; 79.4]) respectively. Intraoperatively, ctDNA detection in portal or peripheral blood was associated with worse RFS (HR[95%CI]3.26[1.26; 8.45],p = 0.010) and OS (HR[95%CI]5.46[1.65;18.01],p = 0.002). Portal vein sampling did not improve ctDNA detection. CtDNA levels were increased by 2.5-fold (p = 0.031) in peripheral blood after tissue mobilization but not significantly linked to RFS or OS. Detecting ctDNA intraoperatively was correlated with poorer RFS (HR [95% CI] 3.26 [1.26;8.45], p = 0.010) and 0S (HR [95% CI] 5.46 [1.65;18.01], p = 0.002). Portal vein sampling did not improve ctDNA detection. Tissue mobilization increases ctDNA levels. Intraoperative detection of ctDNA is associated with a worse prognosis.

Tumor Spread Through Air Spaces Predicts Survival in Resected Pulmonary Lymphoepithelial Carcinoma.

Tumor spread through air spaces (STAS) has been recognized as a prognostic factor for several types of lung cancers. However, information regarding its clinical significance in pulmonary lymphoepithelial carcinoma is limited. Therefore, this study investigated effects of STAS on the clinical outcomes for patients with pulmonary lymphoepithelial carcinoma. This study retrospectively reviewed 56 surgically resected pulmonary lymphoepithelial carcinomas. The study defined STAS as the presence of tumor cells within air spaces in lung parenchyma beyond the tumor edge. Artifacts were excluded. Recurrence-free survival (RFS) was analyzed using the log-rank test and Cox proportional hazards model. In 18 patients (32.1%), STAS was observed and found to be associated with larger tumor size (>3 cm) (p = 0.009), higher pathologic stage (p = 0.026), and tumor necrosis (p = 0.046). Patients with STAS had a significantly lower 5-year RFS rate (p = 0.025). Multivariate analysis showed that STAS was an independent predictor of worse RFS (hazard ratio, 3.395; p = 0.038). Patients with STAS had a significantly increased risk of locoregional recurrence (p = 0.049). The study findings suggest that STAS is an independent predictor of poor RFS. Based on these findings, a new three-tier grading system based on the patterns of tumor border and STAS was proposed for effective prediction of 5-year RFS in pulmonary lymphoepithelial carcinoma.

Combination of grade and spread through air spaces (STAS) predicts recurrence in early stage lung adenocarcinoma: a retrospective cohort study.

Adenocarcinomas, a common subtype of lung cancer, exhibit diverse histological patterns. In 2020, The International Association for the Study of Lung Cancer (IASLC) introduced a grading system emphasizing high-grade components, which has shown prognostic value. Spread through air spaces (STAS) is recognized as a prognostic feature increasing the risk of recurrence in lung cancer. This study evaluates the combination of STAS status and the IASLC-grading system in surgically resected Stage I lung adenocarcinomas. This study is a retrospective analysis of 123 patients with Stage I lung adenocarcinoma who underwent lobectomy between 2011 and 2019. Histological patterns were assessed according to the IASLC criteria, and STAS status was documented. Patients were categorized based on their IASLC Grade and STAS status. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazards models, and comparisons using Chi-square and t-tests. The cohort comprised 43 females and 80 males with a mean age of 61.8 ± 7.6years. STAS positivity was noted in 52.8% of patients. STAS positivity correlated significantly with Grade 3 tumors (p < 0.001). The 5-year recurrence-free survival was significantly lower in STAS-positive patients (70.7% vs. 88.7%, p = 0.026). Patients with Grade 3 and STAS positivity had significantly lower recurrence-free survival compared to other groups (p = 0.002). Grade 3 and STAS positivity were independent predictors of poor recurrence-free survival in multivariate analysis. IASLC Grade 3 tumors and STAS positivity are independent prognostic factors for poor recurrence-free survival in Stage I lung adenocarcinomas. Adjuvant treatment strategies should be considered for patients with these characteristics to improve outcomes.

High Subcutaneous Adipose Tissue Radiodensity Predicts Poor Prognosis in Patients With Gastric Cancer.

Although the impact of body composition on cancer treatment outcomes of patients with cancer has been increasingly reported, it is still unclear whether the radiodensity of subcutaneous adipose tissue (SAT) on computed tomography (CT) images has a prognostic impact on patients with gastric cancer. We measured muscle and SAT profiles on CT and performed an integrated analysis with clinicopathologic factors. We retrospectively analyzed 230 patients with gastric cancer who underwent gastrectomy between June 2016 and December 2020. SAT radiodensity (SAT-R), and skeletal muscle index (SMI) were measured in preoperative CT images. These were compared with clinicopathologic factors, overall survival (OS), and recurrence-free survival (RFS). High SAT-R was significantly associated with older age (p=0.003) and lower BMI, lymphocyte, hemoglobin, γ-GTP, cholinesterase, albumin, and triglyceride values (p<0.001, <0.001, 0.027, 0.032, <0.001, 0.001, and <0.001, respectively). In the univariate analysis, high SAT-R, and low SMI were significantly associated with poor OS (p=0.003 and <0.001) and poor RFS (p=0.014 and 0.011). In the multivariate analysis by Cox proportional hazard model, high SAT-R and low SMI were identified as independent prognostic factors for poor OS (p=0.037 and 0.007). High SAT-R on preoperative CT was associated with poor OS in patients with gastric cancer after gastrectomy. SAT-R has a potential to be a novel prognostic marker for surgically treated patients with gastric cancer.

Long non-coding RNAs as prognostic biomarkers in non-muscle invasive bladder cancer: A systematic review

Traditional prognostic tools for non-muscle invasive bladder cancer (NMIBC) often overestimate progression and recurrence risks, underscoring the need for more precise biomarkers. While long non-coding ribonucleic acids (lncRNAs) have been reviewed in bladder cancer, no review has focused on NMIBC. The aim of this study was to address this gap by investigating the role of lncRNAs in predicting NMIBC survival and progression. A systematic review was conducted using PubMed, Scopus, and Cochrane databases as of July 31, 2024. Prognostic studies investigating the association between lncRNA expression and survival outcomes, such as cancer-specific survival, disease-free survival, recurrence-free survival, or overall survival, using Kaplan-Meier curves or hazard ratios, were included. A total of three studies were analyzed, involving 279 NMIBC patients and focusing on three lncRNAs: urothelial cancer associated 1 (UCA1), growth arrest-specific 5 (GAS5), and up-regulated in non-muscle invasive bladder cancer (UNMIBC). Increased UCA1 expression was strongly associated with poor disease-free survival (hazard ratio (HR): 1.974; 95%CI: 1.061–3.673; p=0.032) and progression-free survival (HR: 3.476; 95%CI: 1.187–10.18; p=0.023). Reduced GAS5 expression was significantly associated with poor disease-free survival (HR: 2.659; 95%CI: 1.348–5.576; p=0.005) and progression-free survival (HR: 6.628; 95%CI: 1.494–29.40; p=0.013). Higher level of UNMIBC was strongly associated with poor recurrence-free survival (HR: 2.362; 95%CI: 1.504–4.837; p=0.007). In conclusion, lncRNAs have potential as prognostic biomarkers in NMIBC, with UCA1 and UNMIBC overexpression and GAS5 underexpression being significant in predicting disease recurrence and progression, highlighting the clinical relevance of monitoring these lncRNAs to improve prognosis and guide treatment decisions.

Genome-wide microRNA Analysis Identified miR-210-3p Over-expression in Pancreatic Cancer Tissues as a Predictor of their Local Invasiveness.

The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor's gene profile is crucial to avoid positive MSM. Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets. Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests. Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes.

NRXN1 as a Prognostic Biomarker: Linking Copy Number Variation to EMT and Survival in Colon Cancer.

The role of biomarkers in cancer treatment varies significantly depending on the cancer stage. Thus, in clinical practice, tailoring biomarkers to meet the specific needs and challenges of each cancer stage can increase the precision of treatment. Because they reflect underlying genetic alterations that influence cancer progression, copy number variation (CNV) biomarkers can play crucial prognostic roles. In our previous study, we identified potential survival-related genes for colorectal cancer (CRC) by analyzing CNV and gene expression data using a machine-learning approach. To further investigate the biological function of NRXN1, we assessed the use of RNA sequencing, phosphokinase assays, real-time quantitative PCR, and Western blot analysis. We found that NRXN1 copy number deletion was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS), even in patients who received adjuvant chemotherapy. Compared with its expression in normal tissues, NRXN1 expression was lower in tumors, suggesting its potential role as a tumor suppressor. NRXN1 knockdown enhanced CRC cell viability and invasion, and transcriptome analysis indicated that the increased invasion was caused by GSK3β-mediated epithelial-mesenchymal transition. These findings highlight NRXN1 copy number deletion as a novel biomarker for predicting recurrence and survival in patients with resected colon cancer.

Association of Perioperative Skeletal Muscle Index Change With Outcome in Colorectal Cancer Patients.

The association between perioperative changes in the skeletal muscle index (SMI) and colorectal cancer (CRC) outcomes remains unclear. We aim to explore perioperative change patterns of SMI and evaluate their effects on long-term outcomes in CRC patients. This retrospective cohort study included Stage I-III CRC patients who underwent curative resection between 2012 and 2019. SMI at the third lumbar vertebra level was calculated using computed tomography scans. Optimal cut-off values for SMI were defined separately for males and females and classified as high or low preoperatively and at 3, 6, 9 and 12 months postoperatively. SMI status was further categorized into different perioperative SMI change patterns: highpre-highpost, highpre-lowpost, lowpre-highpost and lowpre-lowpost. The association with recurrence-free survival (RFS) and overall survival (OS) was examined using Cox proportional hazards models. A total of 2222 patients (median [interquartile range] age, 60.00 [51.00-68.00] years; 1302 (58.60%) men; 222 (9.99%) with preoperative low SMI) were evaluated. During a median follow-up of 60 months, 375 patients (16.88%) died, and 617 patients (27.77%) experienced a recurrence. Multivariate Cox model analysis showed that, compared to patients with highpre-highpost, those with highpre-lowpost (HR = 3.32, 95% CI: 1.60-6.51; HR = 2.54, 95% CI: 1.03-6.26; HR = 2.93, 95% CI: 1.19-7.19, all p < 0.05) had significantly worse RFS and OS (HR = 4.07, 95% CI: 1.55-10.69; HR = 4.78, 95% CI: 1.40-16.29; HR = 9.69, 95% CI: 2.53-37.05, all p < 0.05), at postoperative 6, 9 and 12 months, respectively. Patients with lowpre-lowpost were an independent prognostic factor for worse OS at postoperative 12 months (HR = 3.20, 95% CI: 1.06-9.71, p = 0.040). Patients with lowpre-highpost had similar risk of RFS compared to those with highpre-highpost at postoperative 3, 6 and 12 months (HR = 1.49, 95% CI: 0.75-2.98; HR = 1.05, 95% CI: 0.45-2.43; HR = 1.36, 95% CI: 0.31-6.06, all p > 0.05) and similar risk of OS at postoperative 3, 6, 9 and 12 months (all p > 0.05). Patients with a high preoperative SMI that decline postoperatively have poor RFS and OS. Consistently low SMI also correlates with worse OS. Patients with low SMI but increased after resection are not an indicator of better prognosis. Routine measurement of postoperative, rather than preoperative, SMI is warranted. Patients with low SMI are at an increased risk for recurrence and death, especially within the first year after surgery.

Identification of the Prognostic Factors for Synchronous Multiple Primary Lung Cancer Treated With Staged Bilateral Surgery.

Staged bilateral surgery is widely used to treat synchronous multiple primary lung cancer (SMPLC); however, the prognostic factors for survival outcomes remain unclear. This study aimed to identify prognostic factors and construct a predictive model for overall survival (OS) and recurrence-free survival (RFS) in patients with SMPLC who underwent staged bilateral surgery. The study included 256 patients diagnosed with SMPLC and treated with staged bilateral surgery at our hospital between January 2010 and July 2017. Multivariate Cox proportional-hazard regression was used to identify prognostic factors for OS and RFS. Additionally, a predictive model was constructed using time-dependent receiver operating characteristic curves. Among the 256 patients, 10 (3.95%) succumbed to the disease and 24 (9.41%) experienced recurrence. Smoking (hazard ratio [HR]: 5.128; 95% confidence interval [CI]: 1.442-18.233; p = 0.012) and most advanced pathological TNM (pTNM) stage (II + III) (HR: 12.938; 95% CI: 2.650-63.176; p = 0.002) were identified as significant predictors of poor OS. A prognostic model was developed for predicting OS, with a 5-year area under the curve (AUC) of 0.854. Furthermore, most advanced pTNM stage (II + III) was associated with poor RFS (HR: 5.964; 95% CI: 2.669-13.327; p < 0.001), and the predictive model exhibited a 5-year AUC of 0.718 for RFS. This study revealed that smoking and most advanced pTNM stage were independent prognostic factors associated with poor OS in patients with bilateral SMPLC. Moreover, most advanced pTNM stage was also linked to unfavorable RFS. The developed predictive model demonstrated moderate prognostic performance for both OS and RFS.

Low serum creatine kinase level is associated with poor prognosis in patients with hepatocellular carcinoma: A retrospective single‑center study.

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma.

Gamma-Glutamyl Transpeptidase to Neutrophil Ratio as Prognostic Indicator for Hepatocellular Carcinoma Patients Post-Curative Resection.

The close association between inflammation and the clinical outcomes of hepatocellular carcinoma (HCC) has been extensively documented. This study aims to analyze the association between a novel inflammatory indicator, the gamma-glutamyl transpeptidase to neutrophil ratio (GNR), and HCC prognosis following curative resection. A cohort of 204 eligible HCC cases were included. Based on an optimal cut-off value determined utilizing the X-tile software, patients were categorized into low- and high-GNR groups. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier analysis method with Log rank tests. Multivariate Cox proportional hazard regression was used to investigate the independent association between GNR and HCC prognosis. Restricted cubic splines were used to explore the nonlinear relationship between GNR and the risk of death or recurrence. The low GNR group exhibited significantly higher 3-year OS and RFS rates than the high GNR group. Multivariate Cox analysis indicated that a high GNR level was independently associated with poor OS and RFS. A linear correlation between GNR and the risk of death, as well as a nonlinear inverted "U" shape correlation between GNR and the risk of recurrence, were observed. The findings provide evidence supporting the independent association of GNR with HCC prognosis. These results offer promise for enhancing prognosis assessments and guiding active monitoring strategies for patients with HCC post-curative resection.

Bidirectional association between perioperative skeletal muscle and subcutaneous fat in colorectal cancer patients and their prognostic significance.

Low skeletal muscle mass and high adipose tissue coexist across the body weight spectrum and independently predict the survival ratio of colorectal cancer (CRC) patients. This combination may lead to a mutually exacerbating vicious cycle. Tumor-associated metabolic conditions primarily affect subcutaneous adipose tissue, but the nature and direction of its relationship with skeletal muscle are unclear. This study aims to examine the bidirectional causal relationship between skeletal muscle index (SMI) and subcutaneous fat index (SFI) during the perioperative period in CRC patients; as well as to validate the association between perioperative SMI, SFI, and CRC prognosis. This population-based retrospective cohort study included patients with stage I-III colorectal cancer who underwent radical resection at the Third Affiliated Hospital of Kunming Medical University between September 2012 and February 2019. Based on inclusion and exclusion criteria, 1,448 patients were analyzed. Preoperative (P1), 2 months postoperative (P2), and 5 months postoperative (P3) CT scans were collected to evaluate the skeletal muscle index (SMI; muscle area at the third lumbar vertebra divided by height squared) and subcutaneous fat index (SFI; subcutaneous fat area at the third lumbar vertebra divided by height squared). A random intercept cross-lagged panel model (RI-CLPM) was used to examine the intra-individual relationship between SMI and SFI, and Cox regression was employed to assess the association between SMI, SFI, recurrence-free survival (RFS), and overall survival (OS). The median age at diagnosis was 59.00 years (IQR: 51.00-66.00), and 587 patients (40.54%) were female. RI-CLPM analysis revealed a negative correlation between SFI and subsequent SMI at the individual level: P1-P2 (β = -0.372, p = 0.038) and P2-P3 (β = -0.363, p = 0.001). SMI and SFI showed a negative correlation during P1-P2 (β = -0.363, p = 0.001) but a positive correlation during P2-P3 (β = 0.357, p = 0.006). No significant correlation was found between the random intercepts of SFI and SMI at the between-person level (r = 0.157, p = 0.603). The Cox proportional hazards multivariate regression model identified that patients with elevated SFI had poorer recurrence-free survival (HR, 1.24; 95% CI: 1.00-1.55). Compared to patients with normal preoperative SMI and SFI, those with low SMI or high SFI had poorer recurrence-free survival (HR, 1.26; 95% CI: 1.03-1.55) and overall survival (HR, 1.39; 95% CI: 1.04-1.87). However, no significant association between SMI and SFI and the prognosis of colorectal cancer patients was observed postoperatively. In CRC patients, preoperative muscle loss leads to postoperative fat accumulation, exacerbating muscle loss in a feedback loop. Elevated preoperative SFI predicts poorer survival outcomes. Monitoring SMI and SFI is crucial as prognostic indicators, despite non-significant postoperative associations. Further research is needed to improve patient outcomes.

Prognosis prediction of PDAC via detection of O-glycan altered extracellular vesicles in perioperative sera.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy due to the difficulty in diagnosis and poor prognosis because of the high recurrence rate, necessitating reliable biomarkers to improve the diagnosis and prognosis. However, the existing markers have limitations. We previously identified extracellular vesicles (EVs) recognized by O-glycan-binding lectins (Amaranthus caudatus agglutinin [ACA]) as a novel diagnostic biomarker for PDAC using an EV-counting system (ExoCounter). This retrospective study analyzed changes in ACA-positive EVs in perioperative PDAC serum and its association with prognosis using ExoCounter. Absolute EV levels in the pre- and postoperative sera of 44 patients who underwent curative pancreatectomy for PDAC were quantified using ExoCounter. The carbohydrate antigen 19-9 levels declined in most samples postoperatively, and presented no correlation with poor prognosis. In contrast, ACA-positive EVs increased in serum at 7 days postoperatively in 27 of 44 patients (61.4%). We therefore divided participants with ACA-positive EVs before and after surgery into elevation and decline groups. The overall survival (OS) and recurrence-free survival (RFS) of patients with higher ACA-positive EVs were significantly shorter than those with lower ACA-positive EVs (26.1 months vs. not reached, P = 0.018; 11.9 vs. 38.6 months, P = 0.013). Multivariable analysis revealed that ACA-positive EV elevation in postoperative serum was an independent prognostic factor for poor OS (hazard ratio [HR] = 3.891, P = 0.023) and RFS (HR = 2.650, P = 0.024). The detection of ACA-positive EVs in perioperative serum may be used to predict the prognosis of PDAC in the early postoperative period.

MCT4 is an independent prognostic factor and affects immune cell infiltration in patients with colorectal liver oligometastases.

Monocarboxylate transporter 4 (MCT4) is a novel biomarker related to the level of immune cell infiltration, but its impact on tumor immune microenvironment (TIME) of colorectal liver oligometastases (CLO) remains unclear. The aim of this study was to assess MCT4 expression in primary tumor and liver oligometastases, investigate its impact on immune cell infiltration and its prognostic value for CLO patients undergoing liver resection. We retrospectively selected 135 CLO patients who underwent curative liver resection between June 1999 and December 2016, and samples included 74 primary tumor tissues and 122 liver metastases. Immunohistochemistry (IHC) was performed to detect MCT4 expression in paraffin-embedded specimens and tyramine signal amplification (TSA) was used to detect the density of tumor-infiltrating lymphocytes, including CD3 + , CD8 + and Foxp3 + . Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test, and independent prognostic factors were identified with Cox regression modeling. Survival analysis indicated that CLO patients with low MCT4 expression had better 3-year RFS and 3-year OS rates than those with high MCT4 expression. Multivariate analysis indicated that high MCT4 expression was independently associated with poor RFS and OS. High MCT4 expression was associated with a lower number of intratumoral CD3 + /CD8 + T cells and was associated with higher Foxp3 + T cells infiltration. Patients with low MCT4 expression and high levels of differential immune infiltration had longer survival. MCT4 overexpression was associated with an unfavorable prognosis in patients with CLO and MCT4 expression level had an impact on intratumoral immune infiltration degree. A novel parameter that combined MCT4 expression level and differential immune infiltration level was constructed to stratify patients with CLO into different risk groups.

Myosteatosis and muscle loss impact liver transplant outcomes in male patients with hepatocellular carcinoma.

Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated. Seven hundred fifty-six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non-sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre- and post-LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence-free survival (RFS). The study comprised 673 males and 83 females. The median follow-up time was 31months (interquartile range, 19-43months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low-SMI) and myosteatotic (low-SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5year OS (P<0.001) and a 15.0% decrease in 5year RFS (P=0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317-1.869; P<0.001] and RFS (HR, 1.369; 95% CI, 1.182-1.586; P<0.001). Postoperatively, a muscle loss >14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358-3.849; P=0.002) and RFS (HR, 2.219; 95% CI, 1.418-3.471; P<0.001) in non-sarcopenic recipients (N=209). Pre-transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post-transplant muscle loss might assist in prognostic stratification of recipients without pre-existing sarcopenia, intriguing new insights into individualized management.

Prognostic nutritional index predicts lateral lymph node metastasis and recurrence free survival in papillary thyroid carcinoma

BackgroundPreoperative hematological parameters are predictors of pathological features and recurrence-free survival (RFS) in various malignancies. However, comprehensive studies of preoperative indicators associated with papillary thyroid carcinoma (PTC) are scarce. The present study investigated the association between preoperative indicators and RFS in patients with PTC. Accordingly, we explored the clinical impact of the prognostic nutritional index (PNI) on lymph node metastasis and RFS in patients with PTC.MethodsA total of 619 PTC patients were retrospectively reviewed between Jan 2013 and Dec 2017. Laboratory values were measured and calculated. Receiver operating characteristic curves were generated to calculate the cutoff value. Univariate and multivariate analyses using the COX proportional hazard model were performed for RFS. The effects of PNI and age on RFS were investigated by the Kaplan-Meier method. Clinical characteristics and PNI were tested with the chi-square test. Univariate and multivariate logistic analyses were conducted to evaluate the predictive value of PNI for lymph node metastasis.ResultsIn the multivariate Cox analysis, age, PNI and lymph node metastasis were independent prognostic indicators for RFS. The Kaplan-Meier method showed that the lower PNI group and age older than 55 years group displayed poor RFS. A low preoperative PNI was remarkably correlated with age, sex, extrathyroidal invasion, T stage, N stage and TNM stage. PNI was the only preoperative hematological indicator for lateral lymph node metastasis.ConclusionsAmong the preoperative hematological indicators, PNI may serve as a promising and effective predictor for RFS and lateral lymph node metastasis in PTC patients.

Oncologic outcomes and associated factors of colon cancer patients aged 70 years and older.

The aim of this study was to examine the prognosis and associated risk factors, including adjuvant chemotherapy (CTx), in elderly patients with colon cancer. This retrospective study included patients who underwent radical resection for colon cancer between January 2010 and December 2014 at Asan Medical Center. The effects of stage, risk factors, and chemotherapy on overall survival (OS) and recurrence-free survival (RFS) were compared in patients aged ≥70 and <70 years. Of 3,313 patients, 933 (28.1%) was aged ≥70 years. Of the 1,921 patients indicated for adjuvant CTx, 1,294 of 1,395 patients (92.8%) aged <70 years and 369 of 526 patients (70.2%) aged ≥70 years received adjuvant CTx. Old age (≥70 years) was independently associated with RFS in overall cohort. Among patients aged ≥70 years indicated for adjuvant CTx, the 5-year OS (81.6% vs. 50.4%, P<0.001) and RFS (82.9% vs. 67.4%, P=0.025) rates were significantly higher in those who did than did not receive adjuvant CTx. Additionally, adjuvant CTx was confirmed as independent risk factor of both OS and RFS in patients aged ≥70 years indicated for adjuvant CTx. Old age was associated with poor RFS and adjuvant CTx had benefits in OS as well as RFS in elderly patients eligible for adjuvant CTx.